Real-world challenges for hepatitis C virus medications: a critical overview

Abstract

From 2010, the landscape of hepatitis C therapeutics has been changed rapidly, and today we are standing at a cusp of a pharmacological revolution where highly effective and interferon (IFN)-free direct acting antivirals (DAAs) are already on the market. Such treatment paradigms attain 90-95% sustained virologic response (SVR; undetectable viral load at week 12 or 24 at the end of therapy) rates in treated individuals compared to 50-70% with treatment completion of dual-therapy-pegylated interferon (PEG-IFN) and ribavirin (RBV). As the major goal now for the hepatologists, clinicians, physicians, and health care workers is likely to eradicate hepatitis C infection in parallel to treatment, the demand is for a one-size-fits-all pill that could be prescribed beyond the limitations of hepatitis C genotype, viral load, previous treatment history, advanced hepatic manifestations (fibrosis, cirrhosis) and antiviral drug resistance. Although the new treatment strategies have shown high cure rates in clinical trials, such treatment paradigms are posing dilemmas too in real-world clinical practice. Therapy cost, treatment access to low and middle-income countries, treatment-emergent adverse events, lack of effective viral screening and disease progression simulation models are potential challenges in this prospect. This review article deeply overviews the challenges encountered while surmounting the burden of hepatitis C around the world.

Introductory Chapter: Current and Emerging Anti-Hepatitis C Regimens: Hope or Hype

“…By inhibiting viral replication and blocking polyprotein processing, these novel and innovative DAAs are categorized into four groups, namely, nucleoside RNA-dependent RNA polymerase (RdRp; NS5B protein) inhibitors (NIs), non-nucleoside RdRp inhibitors (NNIs), viral replication complex inhibitors (i.e., NS5A protein), and viral serine protease (i.e., NS3/4A protein) inhibitors (PIs) [1]. Interestingly, the treatment regimens achieve higher sustained virologic response rates (SVR; HCV viral RNA undetectable at the end of week 12) only when used in combination as dual or triple therapeutic regimens, and single DAA therapy is either not so much effective or recommended to use [2]. Some DAAs have been developed as a single pill of fixed dose combination (FDC) of two, three, or even more compounds, and all DAAs are given orally to infected patients.…”

“…Some treatment options with pan-genotypic HCV coverage have been approved by the Food and Drug Administration (FDA) of the United States of America (USA), and some are in the final stage of development. Some different antivirals with an alternate mechanism of action such as by inhibiting viral entry or cell-to-cell spread and some anti-mRNA-based strategies like microRNAs are also in the pipeline [1,2].…”

“…The currently available DAAs are based on their target site with a particular mechanism of action [1,2,13]. NS3-4A serine protease inhibitors (NS3-4A PIs) block posttranslational processing of viral polyproteins by binding to the catalytic site of the enzyme which prevent the release of functional, nonstructural proteins.…”

“…After that a series of innovative DAAs have been approved by the US FDA to treat hepatitis C with excellent SVR rates. The second-generation DAAs in combination are highly effective to treat the wide spectrum of HCV populations, and some have shown clinical promise as pan-genotypic and panfibrotypic coverages [2,13]. The first-generation PIs include telaprevir (TVR) and boceprevir (BOC), while second-generation PIs include simeprevir (SMV), ritonavir-boosted paritaprevir (PTV), asunaprevir (ASV), grazoprevir (GZR), voxilaprevir (VOX), and glecaprevir (GLE).…”

Clustering of hepatitis C virus antibody positivity within households and communities in Punjab, India

“…Direct-acting antivirals (DAAs) have greatly simplified treatment for HCV infection due to ease of administration (all oral regimens), minimal side-effects and high effectiveness [3]. A better understanding of the risk factors driving historical HCV transmission can support targeted screening and linkage to care, which are needed to reach the WHO targets [4]. …”